This is the first part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article explains what alpha thalassemia (AT) is, what causes it and who gets it.

First, the Facts

1. Alpha thalassemia (AT) is a blood condition you are born with. You have to inherit a gene change from both parents to have AT.
2. If you inherit a gene change from one parent, you are a carrier but don’t have the condition. If your partner is also a carrier, you have a chance of having a child with AT.
3. AT is most common in people with ancestry from Southeast and South Asia, Africa, the Middle East and around the Mediterranean.
4. There are two pairs of genes involved in AT – you may have one, two, three or four gene changes. There are also different types of gene changes – the gene can either be missing or damaged.
5. How severe your AT is depends on the number and type of gene changes you have.
6. AT major (four gene changes) is typically fatal before or shortly after birth without intervention. It remains a lifelong condition but can now be managed with treatment.

Thalassemia

Thalassemia is a condition you are born with. It affects red blood cells. There are two main types: alpha thalassemia (AT) and beta thalassemia (BT). This post is about AT.

In AT, the body doesn’t make enough healthy hemoglobin (Hb) and there are too few red blood cells. Hb is the protein in red blood cells that enables them to carry oxygen around the body.

Why Isn’t the Hemoglobin Made Properly?

Hb is the protein molecule in red blood cells that carries oxygen from the lungs to the tissues of the body. Carbon dioxide is also transported by Hb from the tissues back to the lungs. Hb helps maintain the shape of a red blood cell.

Normal adult Hb is made up of four protein chains – two alpha chains and two beta chains. If you have AT, your body either makes abnormal alpha chains or doesn’t produce enough of them, so you can’t make enough healthy Hb.

When there aren’t enough healthy red blood cells and Hb, oxygen does not reach the tissues of the body, and a person can feel weak, tired and have difficulty breathing. This is called anemia. It can be mild or serious. Serious anemia can damage organs and can be fatal.

What Causes AT and Who Gets It?

Causes of AT

AT is a genetic condition. This means it is caused by a change (mutation) in one or more genes. There can be different types of change – some cause the alpha chains of Hb to be missing completely, while others cause a decrease in alpha chain production.

AT is more common in some parts of the world where malaria is, or has been, a problem (for example, the Middle East, northern Africa, India and Southeast Asia) and in people with ancestry originating from these areas. This is because the gene changes that cause AT also give some protection against malaria.

Over time, the proportion of people in the population with an AT gene change has increased and, as people migrate around the world, AT has become more common in other regions too.

Types of AT

The type of AT you have and how it affects you depends on:

• how many genes are changed and which ones
• the combination of genes that are affected
• whether each affected gene is completely missing or damaged.

Four Types of AT

Silent carrier. Blood tests are usually normal. You will often have no symptoms, but you can pass the damaged gene on to your child.

Alpha thalassemia minor/trait. You may have mild anemia with small red blood cells that may be mistaken for iron deficiency anemia. Two genes are affected.

Hemoglobin H (HbH) AT. There is just one working alpha gene. You may have moderate to severe anemia. You have a greater risk of having a child with AT major.

Alpha thalassemia major. All four genes are missing. This causes severe anemia. In most cases, a baby with this condition will die before birth unless they are treated in the womb.

Please check out the other posts of our series here:

• Alpha Thalassemia: Genes, Genetic Inheritance and One Gene Change
• Alpha Thalassemia: Two Gene Changes
• Alpha Thalassemia: Three Gene Changes
• Alpha Thalassemia: Four Gene Changes
• Alpha Thalassemia: Screening and Diagnosis
• Alpha Thalassemia: Symptoms and Treatment
• Alpha Thalassemia: Clinical Trials and New Treatments
• Living with Alpha Thalassemia

Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).